1. Field of the Invention
The present invention relates to a process for producing optically active compounds which are useful as starting materials for physiologically active materials, functional materials and the like, especially to a process for producing optically active .alpha.-hydroxyesters.
2. Description of the Prior Art
Optically active compounds are useful chemical compounds as starting materials or intermediates for physiologically active materials of medical supplies, agricultural chemicals and the like. However, the compounds have optical isomers and in practical use it is necessary to use only one of these antipodes. Further, when racemates or compounds having low optical purity are used, the obtained compounds apparently do not develop enough physiological activity or functionability.
The optically active compounds obtained by the process of the present invention, namely, optically active .alpha.-hydroxyesters are very useful compounds.
From the optically active .alpha.-hydroxyesters, optically active haloesters (B. J. Lee, et al., Tetrahedron, 23, 359(1967), optically active glycols (V. Prelog, et al., Helv. Chim, Acta. 37, 234(1954)), optically active epoxides (K. Mori, et al., Tetrahedron, 35, 933(1979)) and the like which are useful for optically active compounds can be derived. Especially, the optically active epoxides are useful for starting materials for synthesizing ferroelectric liquid crystal compounds which are particularly useful. (Nohira et al. The 12th Forum of liquid crystals, Preprints, 2F11(1986), Nohira et al. The 12th Forum of liquid crystals, Preprints, 1Z02(1987)).
Additionally, the compounds represented by the formula (1) below wherein A is phenyl or a substituted phenyl, which are easily derived by hydrolysis to optically active .alpha.-hydroxyphenylacetic acid or optically active .alpha.-hydroxysubstituted-phenylacetic acid, are useful for optical resolving agents. For example, the compounds are usable for optical resolving agents of medical or agricultural supplies such as 2-amino-1-butanol which is a starting material of antituberculous ethambutol, diltiazem hydrochloride which a coronary vasodilator and tetramizol effective as an anthelmintic (Japanese Patent Publication No. 61-52812, and Japanese Patent Unexamined Publication Nos. 58-32872 and 62-192388).
Further, the compounds are useful for optically resolving agents of .alpha.-amino acids such as alanine, phenyl alanine, methionine, cysteine and the like (Japanese Patent Unexamined Publication Nos. 55-57545 and 60-32752, Japanese Patent Publication No. 58-1105, and Japanese Patent Unexamined Publication Nos. 59-181244, 57-193448 and 59-51239).
Compounds represented by the formula (1) below wherein A is 2-phenylethyl, which are easily derived to 2-amino-4-phenylbutanoates, are starting materials for synthesizing enalapril which is an ACE inhibitor (angiotensinconverting enzyme inhibitor) and the like. ##STR2## (H. Urbach and R. Henning, Tetrahedron Lett., 25, 1143(1984)).
The compounds represented by the formula (I) are useful as described above. However, no effective process for producing optically active compounds is known.
As an example, there is a process of asymmetric reduction of .alpha.-ketoesters with a microorganism or baker's yeast. (K. Nakamura et al., J. Org. Chem., 53, 2589(1988), K. Nakamura et al., Tetrahedron Letters., 29, 2453(1988), Japanese Patent Unexamined Publication No. 62-61587).
However, since the reaction efficiency of these methods are bad and the objective compounds having desired optical purity are not always obtained, these methods are not industrially useful methods.
In chemical reduction of .alpha.-ketoesters, a method wherein optically active .alpha.-hydroxyesters are obtained by using arylglyoxylic acid is reported. However, since the asymmetric yield is very bad (2.4-9.7%ee), it cannot be said that the method is practical (I. Takahashi et al., Chem. Pharm. Bull., 33 3571(1985)).
A method wherein optically active .alpha.-hydroxyesters are obtained by asymmetric reduction with an organic boron compound in a high yield is also reported. However, the organic boron compound is very expensive and a strict reaction condition of a temperature of -78.degree. C. is required. Accordingly, it is difficult to say that the method is industrially useful (H. C. Brown et al., J. Org. Chem., 53, 1231(1988)).
On the other hand, optically active .alpha.-hydroxyesters can be obtained by esterification of optically active carboxylic acids. However, as the .alpha.-hydroxy carboxylic acids obtainable commercially, only lactic acid and mandelic acid are known (K. Motosugi et al., Biotechnol. and Bioeng., 26, 805(1984), Keiichiro Hiyama, Separation Technics, 16 360(1986)). To obtain the other .alpha.-hydroxy carboxylic acids, a method for recrystallizing by using optically active natural alkaloids such as brucine and the like should be used. Namely, salts which are obtained from racemic .alpha.-hydroxy carboxylic acids and natural alkaloids such as brucine and the like are recrystallized. The crystals obtained and salts which are recovered from mother liquor are hydrolyzed in water, respectively, to obtain optically active .alpha.-hydroxy carboxylic acids. However, the method has problems that the recrystallization should be made several times or dozens of times to obtain optically pure .alpha.-hydroxy carboxylic acids and the alkaloids should be recovered. Further, the method for recovering the alkaloids is troublesome. Accordingly, the method is not an advantageous method industrially and economically.
In spite of the usefulness, a better process for producing the optically active .alpha.-hydroxyesters is not known, so that an efficient, economical and technical process is long-desired.
As mentioned above, the efficiency of the conventional methods is very bad, and products having enough asymmetric yield are seldom obtained.